Objectives: The overall objectives of the total project are to study 1) The nature of the metabolic defects in gout, 2) The role of kidneys, 3) Metabolic fate of drugs, 4) Clinical trial of some investigational drugs and 5) Long term study of gout. 1) Many asymptomatic gouty offspring are found to be hyperuricemic, and hyperuricosuric with low ammonium excretion in urine. None is found to have increased PRPP synthetase activity. Two additional cases of partial deficiency of HPRT have been discovered in 2 boys, 4 and 5 years old. Two patients with gout are found to have increased PRPP synthetase activity. 2) Role of kidneys - Studies in 524 gouty patients, and 253 gouty patients with proteinuria reveal deterioration in renal function is largely associated with nongouty causes. 3) Drug metabolism and interaction - Probenecid half life in plasma is prolonged, and its excretion in urine is decreased in presence of pyrazinoic acid. Ascorbic acid is found to compete with uric acid transport. 4) Clinical pharmacology of some investigational drugs - Benzbromarone a potent uricosuric agent is found to be useful in tophaceous gout, and the drug is well tolerated. Halofenate is hypolipidemic and uricosuric. Side effects consist of gastric distress in 5 and skin rash in 2 of the 24 subjects studied. 5) Psychobiological variables associated with onset and recurrence of gouty arthritis were studied in 374 patients, with detailed information in l6. 6) Secondary gout associated with myeloproliferative disorders in 65 cases was reviewed. 7) Clinical material of 1800 cases of primary gout has been programmed, retrieved and utilized for the book on Uric Acid Metabolism and Gout. Bibliographic references: Yu, T. F. and Berger, L. Renal Disease in Primary Gout; A study of 253 gouty patients with proteinuria. Sem Arth Rheum 4:293,1975. Ginsberg, M.H., Genant, H.K., Yu, T.F. and McCarty, D. J. Rheumatoid nodulosis - an unusual variant of rheumatoid disease. Arth Rheum 18:49, 1975.